of entecavir is a single 0.5 mg tablet once-daily for chronic hepatitis
B patients beginning treatment for the first time (nucleoside-na´ve
patients), and a single 1 mg tablet once-daily for patients
Entecavir comes in tablet and oral suspension
forms and is taken by mouth without food. The tablets are film-coated,
triangular-shaped and contain 0.5 or 1.0 mg entecavir.
The oral solution contains 0.05 mg/ml entecavir
in a 260 ml bottle.
Entecavir should be taken 2 hours after a meal
and 2 hours before the next meal. Based on the pharmacokinetic
profile of entecavir after oral dosing, the estimated apparent volume of distribution
is in excess of total body water, suggesting that entecavir is extensively distributed into tissues.
Entecavir is in FDA
Pregnancy Category C. There are no adequate and well-controlled
studies in pregnant women. Reproduction studies have been performed
in rats and rabbits at orally administered doses of 200 and
16 mg/kg/day and showed no embryo-toxicity or maternal toxicity
in rat and rabbit at doses producing systemic exposures approximately
28 and 212 times those achieved at the highest recommended dose
of 1 mg/day in humans.
In rats, maternal
toxicity, embryo-fetal toxicity (resorptions),
lower fetal body weights, tail and vertebral malformations,
reduced ossification (vertebrae, sternebrae, and phalanges), and extra lumbar vertebrae and
ribs were observed at exposures 3,100 times those in humans.
reproduction studies are not always predictive of human response,
entecavir should be used during pregnancy
only if clearly needed and after careful consideration of the
risks and benefits. To monitor fetal outcomes of pregnant women
exposed to entecavir, an Antiretroviral
Pregnancy Registry has been established. Healthcare providers
are encouraged to register patients online at http://www.APRegistry.com
or by calling 1-800-258-4263.
Food and Drug Interactions
of entecavir 0.5 mg with a standard high-fat meal (945 kcal,
54.6 g fat) or a light meal (379 kcal, 8.2 g fat) resulted in
delayed absorption (1.0 to 1.5 hour fed vs. 0.75 hours fasted),
a decrease in Cmax of 44% to 46%, and a decrease in AUC of 18% to 20%. For
this reason, and for best results, it is recommended to take
entecavir 2 hours after a meal and 2 hours before
the next meal.
pharmacokinetics of entecavir following a single 1 mg dose were
studied in patients without chronic hepatitis B infection with
selected degrees of renal impairment. Dosage adjustment is recommended
for patients with a creatinine clearance of less than 50 ml/min, including patients
on hemodialysis or continuous ambulatory
peritoneal dialysis (CAPD). Entecavir
should be administered after hemodialysis.
CAPD removed approximately 0.3% of the dose over 7 days.
Coadministration of the HIV nucleoside/tide analogues with entecavir does not appear to reduce the antiviral efficacy
of entecavir against HBV or of any
of these agents against HBV. In HBV combination assays in vitro,
(Epivir-HBV), (Zerit), (Viread),
were not antagonistic to the anti-HBV activity of entecavir
over a wide range of concentrations. In HIV antiviral assays,
entecavir was not antagonistic to
the in vitro anti-HIV activity of these NRTIs
at greater than 4 times the Cmax of
resistance has been observed among HBV nucleoside analogues.
In cell-based assays entecavir had 8- to 30-fold less inhibition of replication
of HBV that contained lamivudine resistance
mutations rtL180M and rtM204V/I than of wild-type vius.
acidosis and severe hepatomegaly with steatosis, including fatal
cases, have been reported with the use of nucleoside analogues
alone or in combination with antiretrovirals.
Severe acute exacerbations of hepatitis B have
been reported in patients who have discontinued anti-hepatitis
B therapy, including BARACLUDE. Hepatic function should be monitored
closely with both clinical and laboratory follow-up for at least
several months in patients who discontinue anti-hepatitis B
therapy. If appropriate, initiation of anti-hepatitis B therapy
may be warranted.
Limited clinical experience suggests there is
a potential for the development of resistance to HIV (human
immunodeficiency virus) nucleoside reverse transcriptase inhibitors
if BARACLUDE is used to treat chronic hepatitis B virus infection
in patients with HIV infection that is not being treated. Therapy
with BARACLUDE is not recommended for HIV/HBV co-infected patients
who are not also receiving highly active antiretroviral therapy
(HAART). Before initiating BARACLUDE therapy, HIV antibody testing
should be offered to all patients.
BARACLUDE has not been studied as a treatment
for HIV infection and is not recommended for this use.
Dosage adjustment of BARACLUDE is recommended
for patients with a creatinine clearance <50 mL/min, patients
with age-related decreases in renal function, and those on hemodialysis
or continuous ambulatory peritoneal dialysis (CAPD).
Since entecavir is primarily eliminated by the
kidneys, coadministration of BARACLUDE with drugs that reduce
renal function or compete for active tubular secretion may increase
serum concentrations of either entecavir or the coadministered
The safety and efficacy of BARACLUDE in liver
transplant recipients are unknown. Renal function must be carefully
monitored both before and during treatment with BARACLUDE in
a liver transplant recipient who has received or is receiving
an immunosuppressant that may affect renal function, such as
cyclosporine or tacrolimus.
Patients should be advised that treatment with
BARACLUDE has not been shown to reduce the risk of transmission
of HBV to others through sexual contact or blood contamination.
There are no adequate and well-controlled studies
of BARACLUDE administered to pregnant women. BARACLUDE should
be used during pregnancy only if clearly needed and after careful
consideration of the risks and benefits. There are no studies
on the effect of BARACLUDE on transmission of HBV from mother
to infant. Therefore, appropriate interventions should be used
to prevent neonatal acquisition of HBV. Women should be instructed
not to breast-feed if they are taking BARACLUDE.
Safety and effectiveness of BARACLUDE in pediatric
patients below the age of 16 years have not been established.
The most common adverse events of moderate to severe intensity
among patients treated with BARACLUDE in clinical trials included:
headache (4%), fatigue (3%), diarrhea (1%), and dyspepsia (1%).
dose of BARACLUDE is 0.5 mg once daily in nucleoside-naïve
adults, and 1 mg once daily in lamivudine-refractory adults.
BARACLUDE should be administered on an empty stomach (at least
2 hours after a meal and at least 2 hours before the next meal).
The optimal duration of treatment with BARACLUDE for patients
with chronic hepatitis B infection and the relationship between
treatment and long-term outcomes such as cirrhosis and hepatocellular
carcinoma are unknown.